tbuckley/cabot-search huggingface dataset:
Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus–Associated Lower Respiratory Tract Disease in Infants: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023
Authors: Katherine E. Fleming-Dutra, Jefferson M. Jones, Lauren E. Roper, Mila M. Prill, Ismael R. Ortega-Sanchez, Danielle L. Moulia, Megan Wallace, Monica Godfrey, Karen R. Broder, Naomi K. Tepper, Oliver Brooks, Pablo J. Sánchez, Camille N. Kotton, Barbara E. Mahon, Sarah S. Long, Meredith L. McMorrow
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

This report describes the Advisory Committee on Immunization Practices recommendation for the seasonal administration of a single dose of RSV vaccine during weeks 32 through 36 of pregnancy to help prevent severe RSV illness in infants younger than 6 months.
Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study
Authors: Dimitri Aristotle Raptis, Camila Hidlago Salinas, Massimo Malagò
Journal: International Journal of Surgery (2023)

The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes.
ERK mediates interferon gamma-induced melanoma cell death
Authors: Ameya Champhekar, Rachel Heymans, Justin Saco, Guillem Turon Font, Cynthia Gonzalez, Anne Gao, John Pham, June Lee, Ryan Maryoung, Egmidio Medina, Katie M. Campbell, Daniel Karin, David Austin, Robert Damioseaux, Antoni Ribas
Journal: Molecular Cancer (2023)

Abstract Background Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhibition pathway. Methods We performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines to uncover essential nodes in the IFNγ-mediated growth inhibition pathway. We used transcriptomic profiling to identify cell death pathways activated upon IFNγ exposure. Live imaging experiments coupled with apoptosis assays confirmed the involvement of these pathways in IFNγ-mediated cell death. Results We show that IFNγ signaling activated ERK. Blocking ERK activation rescued IFNγ-mediated apoptosis in 17 of 23 (~ 74%) cell lines representing BRAF, NRAS, NF1 mutant, and triple wild type subtypes of cutaneous melanoma. ERK signaling induced a stress response, ultimately leading to apoptosis through the activity of DR5 and NOXA proteins. Conclusions Our results provide a new understanding of the IFNγ growth inhibition pathway, which will be crucial in defining mechanisms of immunotherapy response and resistance.
Small extrachromosomal circular DNA harboring targeted tumor suppressor gene mutations supports intratumor heterogeneity in mouse liver cancer induced by multiplexed CRISPR/Cas9
Authors: Tao Guo, Guo-Qiao Chen, Xu-Fan Li, Meng Wang, Kun-Ming Liu, Xiao-Ying Yang, Si-Cheng Liu, Yi-Li Feng, Peng-Yuan Liu, Hui Lin, An-Yong Xie
Journal: Genome Medicine (2023)

Abstract Background Primary liver cancer has significant intratumor genetic heterogeneity (IGH), which drives cancer evolution and prevents effective cancer treatment. CRISPR/Cas9-induced mouse liver cancer models can be used to elucidate how IGH is developed. However, as CRISPR/Cas9 could induce chromothripsis and extrachromosomal DNA in cells in addition to targeted mutations, we wondered whether this effect contributes to the development of IGH in CRISPR/Cas9-induced mouse liver cancer. Methods CRISPR/Cas9-based targeted somatic multiplex-mutagenesis was used to target 34 tumor suppressor genes (TSGs) for induction of primary liver tumors in mice. Target site mutations in tumor cells were analyzed and compared between single-cell clones and their subclones, between different time points of cell proliferation, and between parental clones and single-cell clones derived from mouse subcutaneous allografts. Genomic instability and generation of extrachromosomal circular DNA (eccDNA) was explored as a potential mechanism underlying the oscillation of target site mutations in these liver tumor cells. Results After efficiently inducing autochthonous liver tumors in mice within 30–60 days, analyses of CRISPR/Cas9-induced tumors and single-cell clones derived from tumor nodules revealed multiplexed and heterogeneous mutations at target sites. Many target sites frequently displayed more than two types of allelic variations with varying frequencies in single-cell clones, indicating increased copy number of these target sites. The types and frequencies of targeted TSG mutations continued to change at some target sites between single-cell clones and their subclones. Even the proliferation of a subclone in cell culture and in mouse subcutaneous graft altered the types and frequencies of targeted TSG mutations in the absence of continuing CRISPR/Cas9 genome editing, indicating a new source outside primary chromosomes for the development of IGH in these liver tumors. Karyotyping of tumor cells revealed genomic instability in these cells manifested by high levels of micronuclei and chromosomal aberrations including chromosomal fragments and chromosomal breaks. Sequencing analysis further demonstrated the generation of eccDNA harboring targeted TSG mutations in these tumor cells. Conclusions Small eccDNAs carrying TSG mutations may serve as an important source supporting intratumor heterogeneity and tumor evolution in mouse liver cancer induced by multiplexed CRISPR/Cas9.
Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer
Authors: Paul Stockhammer, Michael Grant, Anna Wurtz, Giorgia Foggetti, Francisco Expósito, Jianlei Gu, Hongyu Zhao, Jungmin Choi, Sangyun Chung, Fangyong Li, Zenta Walther, Julia Dietz, Emily Duffield, Scott Gettinger, Katerina Politi, Sarah B. Goldberg
Journal: Journal of Thoracic Oncology (2023)

Patients with metastatic EGFR-mutant NSCLC inevitably have disease progression while on tyrosine kinase inhibitor (TKI) therapy. Co-occurring tumor suppressor gene (TSG) alterations have been associated with poor outcomes, however, detailed analyses of their impact on patient outcomes are limited.
Autonomous AI systems in the face of liability, regulations and costs
Authors: Agustina D. Saenz, Zach Harned, Oishi Banerjee, Michael D. Abràmoff, Pranav Rajpurkar
Journal: npj Digital Medicine (2023)

Autonomous AI systems in medicine promise improved outcomes but raise concerns about liability, regulation, and costs. With the advent of large-language models, which can understand and generate medical text, the urgency for addressing these concerns increases as they create opportunities for more sophisticated autonomous AI systems. This perspective explores the liability implications for physicians, hospitals, and creators of AI technology, as well as the evolving regulatory landscape and payment models. Physicians may be favored in malpractice cases if they follow rigorously validated AI recommendations. However, AI developers may face liability for failing to adhere to industry-standard best practices during development and implementation. The evolving regulatory landscape, led by the FDA, seeks to ensure transparency, evaluation, and real-world monitoring of AI systems, while payment models such as MPFS, NTAP, and commercial payers adapt to accommodate them. The widespread adoption of autonomous AI systems can potentially streamline workflows and allow doctors to concentrate on the human aspects of healthcare.
A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma
Authors: Si-Cho Kim, Da-Won Kim, Eun Ju Cho, Jin-Young Lee, Jiwon Kim, Chaesun Kwon, Jeongsil Kim-Ha, Suk Kyun Hong, YoungRok Choi, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Won Kim, Woojin Kim, Hyunsoo Kim, Yoon Jun Kim, Jung-Hwan Yoon, Su Jong Yu, Young-Joon Kim
Journal: Molecular Cancer (2023)

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test's sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.
Impact of glyphosate (Roundup <sup>TM</sup> ) on the composition and functionality of the gut microbiome
Authors: Lauren Walsh, Colin Hill, R. Paul Ross
Journal: Gut Microbes (2023)

Glyphosate, the active ingredient in the broad-spectrum herbicide RoundupTM, has been a topic of discussion for decades due to contradictory reports of the effect of glyphosate on human health. Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) of the shikimic pathway producing aromatic amino acids in plants, a mechanism that suggests that the herbicide would not affect humans as this pathway is not found in mammals. However, numerous studies have implicated glyphosate exposure in the manifestation of a variety of disorders in the human body. This review specifically outlines the potential effect of glyphosate exposure on the composition and functionality of the gut microbiome. Evidence has been building behind the hypothesis that the composition of each individual gut microbiota significantly impacts health. For this reason, the potential of glyphosate to inhibit the growth of beneficial microbes in the gut or alter their functionality is an important topic that warrants further consideration.
Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches
Authors: Nazeer Hasan, Arif Nadaf, Mohammad Imran, Umme Jiba, Afsana Sheikh, Waleed H. Almalki, Salem Salman Almujri, Yousuf Hussain Mohammed, Prashant Kesharwani, Farhan Jalees Ahmad
Journal: Molecular Cancer (2023)

Abstract Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed. Graphical Abstract
A LIGHTFUL nanomedicine overcomes EGFR-mediated drug resistance for enhanced tyrosine-kinase-inhibitor-based hepatocellular carcinoma therapy
Authors: Ke Yi, Huimin Kong, Chunxiong Zheng, Chenya Zhuo, Yuanyuan Jin, Qingguo Zhong, Rachel L. Mintz, Enguo Ju, Haixia Wang, Shixian Lv, Yeh-Hsing Lao, Yu Tao, Mingqiang Li
Journal: Biomaterials (2023)
Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation
Authors: Kangchun Wang, Xin Wang, Qi Pan, Bei Zhao
Journal: Molecular Cancer (2023)

Abstract Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.
Metabolic support by macrophages sustains colonic epithelial homeostasis
Authors: Stephanie Deborah Fritsch, Nyamdelger Sukhbaatar, Karine Gonzales, Alishan Sahu, Loan Tran, Andrea Vogel, Mario Mazic, Jayne Louise Wilson, Stephan Forisch, Hannah Mayr, Raimund Oberle, Jakob Weiszmann, Martin Brenner, Roeland Vanhoutte, Melanie Hofmann, Sini Pirnes-Karhu, Christoph Magnes, Torben Kühnast, Wolfram Weckwerth, Christoph Bock, Kristaps Klavins, Markus Hengstschläger, Christine Moissl-Eichinger, Gernot Schabbauer, Gerda Egger, Eija Pirinen, Steven H.L. Verhelst, Thomas Weichhart
Journal: Cell Metabolism (2023)

The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals" that provide metabolic support to promote efficient self-renewal of the colon epithelium.
HIV-1 neutralizing antibodies provide sterilizing immunity by blocking infection of the first cells
Authors: Viktoria Stab, Christiane Stahl-Hennig, Armin Ensser, Elie Richel, Kirsten Fraedrich, Ulrike Sauermann, Bettina Tippler, Florian Klein, Dennis R. Burton, Matthias Tenbusch, Klaus Überla
Journal: Cell Reports Medicine (2023)

Neutralizing antibodies targeting HIV-1 Env have been shown to protect from systemic infection. To explore whether these antibodies can inhibit infection of the first cells, challenge viruses based on simian immunodeficiency virus (SIV) were developed that use HIV-1 Env for entry into target cells during the first replication cycle, but then switch to SIV Env usage. Antibodies binding to Env of HIV-1, but not SIV, block HIV-1 Env-mediated infection events after rectal exposure of non-human primates to the switching challenge virus. After natural exposure to HIV-1, such a reduction of the number of first infection events should be sufficient to provide sterilizing immunity in the strictest sense in most of the exposed individuals. Since blocking infection of the first cells avoids the formation of latently infected cells and reduces the risk of emergence of antibody-resistant mutants, it may be the best mode of protection.
A new research agenda for African generative AI
Authors: Rachel Adams, Ayantola Alayande, Zameer Brey, Brantley Browning, Michael Gastrow, Jerry John Kponyo, Dona Mathew, Moremi Nkosi, Henry Nunoo-Mensah, Diana Nyakundi, Victor Odumuyiwa, Olubunmi Okunowo, Philipp Olbrich, Nawal Omar, Kemi Omotubora, Paul Plantinga, Gabriella Razzano, Zara Schroeder, Andrew Selasi Agbemenu, Araba Sey, Kristophina Shilongo, Shreya Shirude, Matthew Smith, Eric Tutu Tchao, Davy K. Uwizera
Journal: Nature Human Behaviour (2023)
FedFTN: Personalized federated learning with deep feature transformation network for multi-institutional low-count PET denoising
Authors: Bo Zhou, Huidong Xie, Qiong Liu, Xiongchao Chen, Xueqi Guo, Zhicheng Feng, Jun Hou, S. Kevin Zhou, Biao Li, Axel Rominger, Kuangyu Shi, James S. Duncan, Chi Liu
Journal: Medical Image Analysis (2023)
OBIA: An Open Biomedical Imaging Archive
Authors: Enhui Jin, Dongli Zhao, Gangao Wu, Junwei Zhu, Zhonghuang Wang, Zhiyao Wei, Sisi Zhang, Anke Wang, Bixia Tang, Xu Chen, Yanling Sun, Zhe Zhang, Wenming Zhao, Yuanguang Meng
Journal: Genomics Proteomics & Bioinformatics (2023)

With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia.
Real-World Genomic Profile of EGFR Second-Site Mutations and Other Osimertinib Resistance Mechanisms and Clinical Landscape of NSCLC Post-Osimertinib
Authors: Julia K. Rotow, Jessica K. Lee, Russell W. Madison, Geoffrey R. Oxnard, Pasi A. Jänne, Alexa B. Schrock
Journal: Journal of Thoracic Oncology (2023)

The emergence of osimertinib as standard of care for EGFR-mutant NSCLC has renewed the need to understand and overcome drug resistance. We sought to understand the genomics and real-world treatment landscape of NSCLC with EGFR C797S and other on- and off-target resistance mechanisms. Comprehensive genomic profiling (CGP) results from tissue or blood samples from 93,065 patients with NSCLC were queried for osimertinib EGFR second-site resistance mutations (ssEGFRms; C797, L718, G724, G796, L792). A real-world electronic health record-derived deidentified clinicogenomic database of patients with NSCLC undergoing CGP from approximately 280 U.S. cancer clinics was queried to assess post-osimertinib resistance and clinical treatment outcomes. A ssEGFRm was identified in 239 of 8845 (2.7%) EGFR-driven (L858R or exon 19 deletion) NSCLCs, most frequently C797 (71%), L718 (15%), and G724 (9.5%). ssEGFRms were not equally distributed across drivers; C797 and G724 changes strongly favored exon 19 deletion and L718, G796 and L792 favored L858R. Post-osimertinib CGP detected ssEGFRm in 19% of the cases (39 of 205); in paired pre-/post-osimertinib samples, on- and off-target resistance was largely mutually exclusive and observed in 24% and 27% of the cases, respectively. Of 391 patients with post-osimertinib treatment data, 62% received a chemotherapy-based regimen, whereas 25% received a targeted therapy or clinical study drug. Median real-world overall survival was 11.4 months from osimertinib progression. The osimertinib resistance landscape is diverse with on-target ssEGFRm and off-target resistance detected in tissue and liquid biopsy. Post-osimertinib, patients are receiving primarily chemotherapy-based regimens with poor outcomes, and CGP at resistance may offer an opportunity to inform therapeutic development and improve treatment selection.
Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials
Authors: Axel Dignass, Wolfgang Stremmel, Marek Horyński, Oleksandr Poyda, Peter Armerding, Klaus Fellermann, Jost Langhorst, Tanja Kuehbacher, Peter Uebel, Juergen Stein, Gottfried Novacek, Elena Avalueva, Oleksandr Oliinyk, Peter Hasselblatt, Andrey Dorofeyev, Heidrun Heinemann, Ralph Mueller, Roland Greinwald, Walter Reinisch
Journal: Clinical Gastroenterology and Hepatology (2023)
Characterizing the mechanisms of social connection
Authors: Mauricio R. Delgado, Dominic S. Fareri, Luke J. Chang
Journal: Neuron (2023)

Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the epidemic of loneliness and the myriad protective benefits conferred by social connection. In this review, we highlight the psychological and neural mechanisms that enable us to connect with others, which in turn help buffer against the consequences of stress and isolation. Central to this process is the experience of rewards derived from positive social interactions, which encourage the sharing of perspectives and preferences that unite individuals. Sharing affective states with others helps us to align our understanding of the world with another's, thereby continuing to reinforce bonds and strengthen relationships. These psychological processes depend on neural systems supporting reward and social cognitive function. Lastly, we also consider limitations associated with pursuing healthy social connections and outline potential avenues of future research.
Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial–mesenchymal transition pathways
Authors: T. Ottone, G. Silvestrini, R. Piazza, S. Travaglini, C. Gurnari, F. Marchesi, A. M. Nardozza, E. Fabiani, E. Attardi, L. Guarnera, M. Divona, P. Ricci, M. A. Irno Consalvo, S. Ienzi, R. Arcese, A. Biagi, L. Fiori, M. Novello, A. Mauriello, A. Venditti, L. Anemona, M. T. Voso
Journal: Leukemia (2023)